Biochem Post-midterm Mitochondrial function

• Cytosol: glycolysis, pentose phosphate shunt, fatty acid synthesis
• Mitochondrial matrix: citric acid cycle, oxidative phosphorylation, B-oxidation of fatty acids, ketone body formation
• Both compartments: gluconeogenesis, urea synthesis

Acetyl-CoA + 3 NAD+ + FAD + GDP + Pi+ 2 H2O-> 

2 CO2+ 3NADH + FADH2 + GTP + 2H+ + CoA

• A-ketoglutarate -> amino acids
• Succinyl CoA-> porphyruns
• Oxaloacetate-> amino acids and phosphoenol pyruvate (that can make glucose)
• Pyruvate -> Oxaloacetate (using ATP Co2)

Any step that requires NAD+ or FAD  (4 steps)

• Acetyl-CoA-> Citrate, inhibited by ATP , acetyl CoA, and NADH
• Isocitrate-> a-ketoglutarate, inhibited by ATP, promoted by ADP
• A-ketoglutarate-> Succinyl CoA, inhibited by succinyl CoA and NADH

• NADH
• O2

• 1= NADH-Q Reductase
• 2= Q (Succinate: Q reductase)
• 3= Cytochrome reductase
• Cytochrome C (transfers an electron between 3 and 4)
• 4= Cytochrome oxidase

Mitochondria have evolved from aerobic bacteria which were phagocytosed by eukaryote cells at the time oxygen appeared on earth

similarities between mitochondria and bacteria:  cardiolipin, transporters, ribosomes, circular DNA+ RNA

Tetracycline and chloroamphenicol (antibiotics)

• extensive use of these drugs can inhibit
• a) bone marrow mitochondrila protein synthesis leading to decreased production of white or red blood cells
• 2. intestinal epithelium cell division.

• NADH-> NAD
• Q-> QH2

• Iron sulfur protein
• Q(Ubiquinone) reduced to QH2(Ubiquinol through a semi-quinone intermediate

• Cytochome C Reductase
• Iron sulfur protein bound to a heterodimer (Cyt C and Cyt B)

• QH*-> Q
• Cyt Fe+3 -> Cyt Fe+2

• Located on the inner mitochondrial membrane
• Cytochrome C binds this and Complex 3

• 4H+ + O2 -> 2H2O
• Sends 4 hydrogens across the membrane(from the matrix to the intermembrane space) to establish gradient used by ATP synthase

rotenone and amytal= NADHQ Reductase -> QH2

antimycin= Cytochrome B-> Cytochrome C1

(cyanide)CN-, N3-(azide), CO (carbon monoxide) = Cytochrome oxidase-> O2

Consists of heme group attached to sulfur above the plan, and nitrogen below the plane (Met80, His18)

Heme group in cytochrome C is covalently attached to 2 cysteine side-chains by thioester linkages (Vinyl group + Cysteine-> Thioester linkage)

• Electron transport for ATP production
• Major cause of most programmed cell death when cytochrome C is released into the cytosol

• 26/104 a.a. have been invariant for 1.5 *10^9 years
• Met 80 and His 18 co-ordinate Fe of the heme
• 11 residues from 70-80 are unchanged/invariant throught all cytocome C's (these residues create a hydrophobic crevice)
• a number of invariant arginine and lysine clusters can b found on the surface of the protein

Pumps protons out of the matrix to establish a gradient, protons will flow down their gradient to generate ATP using ATP synthase

When ADP is readily available, the functioning of the ETC increases

• Cytosolic NADH oxidation (allows NADH produced in cytosol to further enhance oxidative phosphorylation)
• Acetyl CoA (NADPH export)(Isocitrate, and Citrate can leave to increase NADPH in cytosol for drug metabolism/fatty acid synthesis) 
• Transport systems of mitochondria
• Gluconeogenesis and glucose transport (malate can leave and eventually turn into glucose)

creatine stored in muscles and makes ATP - enhances performance in certain repetitive, high intensity, short-term exercise tasks. Offsets fatigue in mitochondrial myopathy patients and improves the mobility of the elderly

• -an essential electron and proton carrier in the mitochondrial respiratory chain
• -found in all intracellular membranes
• -acts as an antioxidant
• -synthesized in mitochondria- deficiency may occur in patients taking cholesterol lowering drugs

• Converts pyruvate to Acetyl-CoA (enters the CAC)
• Nad+ -> NADH
• CoA-SH -> CO2

• Inhibit aconitase, this can cause a buildup in citrate
• Buildup of citrate will cause:
• -complexing with iron 
• -lack of shuttling of isocitrate to detoxify drugs
• -lack of ETC/citric acid cycle functioning